In Caenorhabditis elegans, the let-7 miRNA regulates the exit of cell cycle and terminal differentiation at the L4-to-adult switch. Dysfunction of let-7 results in irregular hypodermal and vulval development of C. elegans and is also a feature of human lung cancer. Here we show that Receptor of Activated C Kinase (RACK-1) modulates let-7-mediated regulation in C. elegans. The RACK-1 protein co-immunoprecipitated with the nematode Argonaute protein, ALG-1. Reduction of rack-1 gene expression by RNAi suppressed the aberrant vulva and hypodermis development phenotypes of let-7(n2853) mutant animals and promoted adult-specific gene expression. Our results indicate a relationship between RACK-1 and let-7 in regulation of terminal differentiation that may help understand the mechanism of translational control by miRNAs.